Trial Information

Phase II Clinical Trial of Tumour Vaccination By Intradermal Delivery of Autologous Dendritic Cells Transduced With Adenoviral Vector (AD5F35) Expressing Latent Membrane Protein-1 (LMP-1) and Latent Membrane Protein-2 (LMP-2) Genes in Combination With Celecoxib in Patient With Metastatic Nasopharyngeal Carcinoma

OBJECTIVES:

Primary

- To evaluate the clinical benefit rate (complete response, partial response, and stable
disease for ≥ 14 weeks) in patients with metastatic nasopharyngeal carcinoma treated
with autologous dendritic cells (DC) transduced with AD5F35 expressing LMP-1 and LMP-2
when administered in combination with celecoxib.

Secondary

- To evaluate the toxicities of this regimen in these patients.

- To evaluate the specific T-cell response against LMP-1 and LMP-2 as measured by HLA
tetramer technology, ELISPOT assay, and delayed-type hypersensitivity in patients
treated with this regimen.

- To evaluate the surrogate tumor marker response plasma EBV DNA by real-time PCR in
these patients.

- To evaluate and characterize immunological cell types and tumor characteristics in
biopsy specimens of patients treated with this DC vaccine and compare it with
pre-vaccine biopsy specimens.

- To evaluate progression-free survival and overall survival of patients who show initial
clinical benefit to DC vaccine.

OUTLINE: Patients undergo blood collection for the preparation of the autologous dendritic
cell (DC) vaccine. Immature DCs are transduced with latent membrane protein-1 (LMP-1) and
latent membrane protein-2 (LMP-2) using the adenoviral vector 5F35. Beginning 1 week after
blood collection, patients receive vaccination with autologous DCs transduced with
AD5F35-LMP-1/LMP-2 intradermally every 2 weeks for a total of 5 vaccinations. Patients also
receive celecoxib twice a day beginning 1 week before the first vaccination and continuing
for up to 6 weeks after completion of the last vaccination.

Patients who demonstrate clinical benefit after completion of 5 courses of vaccination may
continue to receive the DC vaccine alone off study every 2 weeks until disease progression
(based on CT scan findings) or at the investigator's discretion.

Patients undergo blood and tumor tissue sample collection periodically for laboratory
studies. Blood samples are analyzed using MHC tetramer analysis; enzyme-linked immunospot
(ELISPOT) analysis; EBV DNA titers to assess response; and flow cytometry to assess
lymphocyte kinetics. Tumor tissue samples are used for immunological studies. Delayed-type
hypersensitivity is also assessed.

After completion of study treatment, patients are followed monthly for up to 1 year.